Table 4

Safety and efficacy of ocrelizumab in lupus nephritis: design and results of the BELONG study

Patients and methods

Concomitant therapy

Endpoints

Results

A total of 381 patients with class III or class IV (80%) LN were randomised equally to receive either: placebo, OCR 400 mg or OCR 1,000 mg on days 1, 15 and every 16 weeks thereafter, >74% received three infusions and >50% received four infusions

In addition, either: MMF up to 3 g/day (63%); or EL (cyclophosphamide 500 mg ×6/2 weeks) followed by azathioprine 2 mg/kg up to 200 mg/day; and a steroid taper regimen - intravenous steroids: allowed up to 3 g by day 15, given in divided pulses), oral steroids: 0.5 to 0.75 mg/kg (≤60 mg/day) with taper to ≤10 mg over 10 weeks

Complete renal response: normal serum creatinine and ≤25% higher than baseline; urinary protein to creatinine ratio <0.5; inactive urinary sediment

In all modified intention-to-treat populations, there was a treatment difference of 12.2% with 54.7% vs. 66.9% for placebo (n = 75) and OCR (n = 148) groups, respectively

Partial renal response: serum creatinine ≤25% above baseline value; and 50% improvement in the urine protein to creatinine ratio, and if baseline ratio >3.0 then a urine protein to creatinine ratio <3.0

ORR higher in OCR (400 mg) + EL (65.6%) and OCR (1,000 mg) + EL (74.2%) groups vs. placebo + EL (42.9%), ORR was similar in OCR+ MMF (67.9%) vs. placebo + MMF (61.7%)

Nonresponse: not achieving either a complete or partial renal response. Patients who died or discontinued the study prior to week 48 (and had no renal data within 12 weeks of week 48) were considered nonresponders

≥50% reduction in urine protein-to-creatinine ratio occurred in 69.6% vs. 58.7 % for OCR and placebo groups, respectively

Urine protein-to-creatinine ratio <0.5 was achieved in 39.9% vs. 37.3% for

OCR and placebo, respectively

Serious adverse effects imbalance

appeared to be driven by the combination with MMF: OCR 400 mg (41.8%) compared with 1,000 mg OCR + MMF (24.1%) and placebo + MMF (21.3%). Serious adverse event rates in EL groups were not reported as higher in the OCR arms

Serious infection imbalance appeared to be driven by the OCR combination with MMF. MMF groups: OCR 400 mg (32.9%) compared with 1,000 mg OCR (19%) and placebo + MMF (16.3%). EL groups: OCR 400 mg (12.8%) compared with 1,000 mg OCR (10.4%) and placebo + MMF (11.1%)

EL, EUROLUPUS regimen (cyclophosphamide followed by azathioprine); LN, lupus nephritis; MMF, mycophenolate mofetil; OCR, ocrelizumab; ORR, overall renal response.

Reddy et al. Arthritis Research & Therapy 2013 15(Suppl 1):S2   doi:10.1186/ar3910